Rotenone and 1-methyl-4-phenyl pyridinium (MPP+) are two mitochondrial
neurotoxins known to produce
Parkinson's disease (PD) in experimental animals. In the present study, we compared drug-induced rotational asymmetry in rats lesioned using these
neurotoxins at three distinct basal ganglia sites, the striatum, substantia nigra pars compacta (SNpc) and median forebrain bundle (MFB). The levels of
dopamine (DA) in the ipsilateral striata of these hemiparkinsonian animals were assayed employing an HPLC-electrochemical procedure 2 days after the final rotational study. Rats infused with
rotenone or MPP+ into the SNpc, but not into the striatum or MFB, exhibited contralateral rotations immediately after recovery from
anesthesia. Irrespective of the lesion site or the toxin used, all the animals exhibited ipsilateral rotations when challenged with
D-amphetamine.
Apomorphine administration caused contralateral circling behavior in MFB-lesioned animals, but ipsilateral rotations in rats that received
rotenone or MPP+ in the striatum or SNpc. Stereotaxic administration of
rotenone into the MFB, SNpc or striatum caused a significant loss of DA in the ipsilateral striatum to varying degrees (96%, 62% and 30%, respectively, as compared to the contralateral side). However, unilateral MPP+ administration into the MFB, SNpc or striatum caused respectively about 98%, 74% and 59% loss of striatal DA. Behavioural observations and the neurochemical results indicate that, among the three anatomically distinct loci-lesioned, MFB-lesioned animals mimicked behavioral aberrations similar to nigral lesions caused by
6-hydroxydopamine, a classical parkinsonian
neurotoxin. Moreover, the results point out that while both
d-amphetamine and
apomorphine-induced rotations could be considered as valuable behavioral indices to test novel drugs against PD, yet
apomorphine-induced contralateral bias proves to be a more reliable
indicator of specific destruction in the nigrostriatal pathway and development of post-synaptic DA receptor supersensitivity.